Method for measuring hemoglobin concentration ( hgb) in the blood in a circuit of a dialysis machine, measuring device and circuit for the application of the method

ABSTRACT

A method for measuring the hemoglobin concentration (HGB) in the blood in a circuit ( 2 ) of a dialysis machine ( 1 ), the method comprising the measurement of the values of absorption (A) of electromagnetic waves by the blood conveyed along a specified section ( 5   a ) of the said circuit ( 2 ), the measurement of the values of a physical quantity iron the group comprising the blood pressure ( 1 )), the blood temperature (T) and the rate of flow (Q b ) of the blood along the aforesaid section ( 5   a ), and the calculation of the hemoglobin concentration (HGB) as a function of the values of absorption (A) and of the aforesaid physical quantity

DESCRIPTION

[0001] The present invention relates to a method for measuringhemoglobin concentration in the blood in a circuit of a dialysismachine.

[0002] Generally, a dialysis machine of the known type comprises a firstcircuit for blood circulation, connected, when in use, to thecirculatory system of a patient, a second circuit for the circulation ofdialysate, and a filter, through which the first circuit passes theblood and the second circuit passes the dialysate. The filter comprisesa semi-permeable membrane which, when in use, separates the dialysatefrom the blood, and permits an exchange of ions between the dialysateand the blood and the transfer of some of the blood plasma through themembrane. The first circuit comprises an arterial branch located up-linefrom the filter and a venous branch located down-line from the filter,while the machine comprises a peristaltic pump located in the arterialbranch to convey the blood extracted from the patient to the filter. Thefirst and second circuits are made from transparent flexible material,such as PVC, to ensure the a sepsis of the circuit. The flexibility ofthe circuits facilitates their packaging and enables the flow to beblocked by a simple constriction of a section of the circuit, while thetransparency makes it possible to visually inspect the liquids beingconveyed in the circuit during use

[0003] There is a known way of determining the concentration ofhemoglobin in the red corpuscles during the dialysis treatment, by meansof highly accurate measurements of an intrusive kind, which require thelaboratory examination of blood samples. Other dialysis machines enablenon-intrusive measurements of the hemoglobin concentration to be madewithin the machine. The non-intrusive measurements made within themachine are markedly less accurate than laboratory measurements, buthave the advantage of being provided in real time in such a way that theoperating parameters of the dialysis machine can be correctedinstantaneously.

[0004] The patent IT 1,240,489 discloses a method of measuring thehemoglobin concentration within the machine and in a non-intrusive way,by measuring the absorption of electromagnetic waves of the bloodflowing in the arterial branch of the first circuit.

[0005] Hemoglobin is a protein contained in the red corpuscles, and itsconcentration modifies the pigmentation of the red corpuscles; theconcentration of hemoglobin in the blood therefore depends on thequantity of red corpuscles contained in the blood and on the quantity ofhemoglobin contained in the red corpuscles. To measure the absorption ofelectromagnetic waves by the blood, an emitter is used to emit a beam ofelectromagnetic waves having an emission intensity correlated with anemission signal, the beam of electromagnetic waves is made to strike asection of the circuit, and a beam of electromagnetic waves is detectedby means of a receiver which emits a signal correlated with thereception intensity. The difference between the emitted intensity andthe received intensity corresponds to the absorption, which iscorrelated with the hemoglobin concentration by a specific function.

[0006] Although the described method has been shown to provide anaccurate measurement, laboratory tests conducted by the applicant havedemonstrated that, in some cases of operation of the dialysis machine,the measurement made according to the method described above suppliesvalues of hemoglobin concentration which deviate from the concentrationvalues measured in the laboratory for the same type of blood.

[0007] The object of the present invention is to provide a method formeasuring the hemoglobin concentration in the blood in a circuit of adialysis machine in a non-intrusive way, and with a level of accuracywhich is as close as possible to the level of accuracy of laboratorymeasurement.

[0008] According to the present invention, a method is provided formeasuring the hemoglobin concentration in the blood in a circuit of adialysis machine, the method comprising the measurement of theabsorption of electromagnetic waves by the blood along one section ofthe said circuit, the values of the said absorption being correlatedwith the values of the said hemoglobin concentration; the method beingcharacterized in that the values of at least one physical quantity ofthe blood, from the group comprising blood pressure, blood temperatureand the rate of flow of blood along the said section, are measured, andthe values of hemoglobin concentration in the blood are calculated as afunction of the values of absorption and of the said physical quantity.

[0009] The present invention also relates to a circuit for theapplication of the aforesaid method.

[0010] According to the present invention, a blood circulation circuitfor a dialysis machine is provided for the application of the methodaccording to at least one of claims 1 to 12, characterized in that itcomprises a connection forming the said section of the circuit, the saidconnection comprising a tube for subjecting the blood to the measurementof the absorption of electromagnetic waves and a chamber for subjectingthe blood to the measurement of pressure.

[0011] The present invention relates to a device for measuring acharacteristic of the blood in a circuit of a dialysis machine.

[0012] According to the present invention, a device is provided formeasuring the hemoglobin concentration in a circuit of a dialysismachine comprising a connection forming a section of the said circuit,the said connection comprising a tube along which a measurement is madeby means of beams of electromagnetic waves to determine the absorptionof the blood, the hemoglobin concentration being correlated with thesaid absorption, the device being characterized in that it comprises atleast one further sensor for measuring one of two quantities, namely theblood pressure and the blood temperature; the hemoglobin concentrationbeing a function of the absorption and of the said quantity.

[0013] The present invention will now be described with reference to theattached drawings, which show, without restrictive intent, an example ofembodiment in which

[0014]FIG. 1 is an experimental graph showing the hemoglobinconcentration as a function of the received intensity;

[0015]FIG. 2 is an experimental graph showing the error of measurementof the hemoglobin concentration as a function of the blood temperature;

[0016]FIG. 3 is an experimental graph showing the error of measurementof the hemoglobin concentration as a function of the blood pressure;

[0017]FIG. 4 is an experimental graph showing the error of measurementof the hemoglobin concentration as a function of the blood flow;

[0018]FIG. 5 is a schematic view of a dialysis machine for implementingthe method according to the present invention;

[0019]FIG. 6 is a side elevation of an element of the device forimplementing the present invention;

[0020]FIG. 7 is a plan view of the element of FIG. 6;

[0021]FIG. 8 is a graph of received intensity as a function of time in afirst operating condition of the machine of FIG. 5; and

[0022]FIG. 9 is a graph of received intensity as a function of time in asecond operating condition of the machine of FIG. 5.

[0023] With reference to FIG. 5, the number 1 indicates the whole of adialysis machine for carrying out dialysis treatments on patientssuffering from kidney failure. The machine 1 comprises a blood circuit2, a dialysate circuit 3, and a filter 4. In use, the circuit 2 isconnected to the circulatory system of a patient and supplies the bloodtaken from the patient to the filter 4 along an arterial branch 5 andreturns the blood to the patient along a venous branch 6. The filter 4comprises a semi-permeable membrane 7, which separates the blood fromthe dialysate and permits an exchange of ions between the blood and thedialysate and the extraction of some of the blood plasma from the bloodcircuit 2. The machine 1 comprises a peristaltic pump 8, which islocated on the arterial branch 5 and, in use, extracts the blood fromthe patient and conveys the blood to the filter 4, and a measuringdevice 9 for measuring hemoglobin concentration (HGB) in the blood alongthe arterial branch 5 in a non-intrusive way.

[0024] The measuring device 9 comprises a connection 10 located betweenthe peristaltic pump 8 and the filter 4, a sensor 11 of the opticaltype, a pressure sensor 12, a temperature sensor 13 and a calculationunit 14 connected to the sensors 11, 12 and 13. With reference to FIG.1, the connection 10 forms a section 5 a of the arterial branch 5 and isinterposed between two flexible sections 5 b and 5 c of the arterialbranch 5.

[0025] With reference to FIGS. 6 and 7, the connection 10 comprises atube 15 and a chamber 16 rigidly connected to the tube 15; the tube 15is integral with the chamber 16 and both are made from transparent rigidplastic. The chamber and/or the tube may integrally carry a radialelement protruding from the surface of connection 10 in the form of alittle fin (not shown) that may serve to easily handle the connector andas positioning device to easily mount and fix the connector onto amachine. The tube 15 comprises an opening 17 for connection to thesection 5 b, an opening 18 for connection to the section 5 c, a portion19 adjacent to the chamber 16 and a portion 20, which has an internaldiameter Di and is located between the opening 17 and the portion 19.The chamber 16 comprises a container 21, a cover 22 provided with acentral hole 23 and an elastic membrane 24, which is gripped between thecontainer 19 and the cover 22 and is deformed as a function of the bloodpressure. In other words, the pressure sensor 12 comprises the chamber16 and an electric device 25 for measuring the extent of deformation ofthe membrane 24 in the form of an electrical signal acquired by thecontrol unit 14.

[0026] The sensor 11 comprises an emitter 26 for emitting a beam ofelectromagnetic waves in the visible, or “NIR”, spectrum, and forguiding the beam of electromagnetic waves along the portion 18 of thetube 14 and a detector 27 for receiving a beam of electromagnetic waveson the opposite side of the tube 14. The sensor 11 is described indetail in the patent IT 1,240,489, whose content is included byreference in the present description.

[0027] The temperature (T) sensor 13 is a sensor of electromagneticwaves which are outside the visible or NIR spectrum.

[0028] In use, the peristaltic pump 8 provides a flow of blood Q_(b)along the circuit 2 as indicated by the arrow in FIG. 1 and through theconnection 10. The peristaltic pump 8 supplies the values of the flowQ_(b) to the controller 13 at successive instants.

[0029] The sensor 12 transmits electrical signals correlated to thepressure values P at successive instants to the calculation unit 14,while the sensor 13 supplies electrical signals correlated with thevalues of temperature T to the calculation unit 14. The blood flowingalong the portion 20 of the tube 15 forms an optical path which iscorrelated with the internal diameter Di of the portion 20, while thedetector 27 receives a beam of electromagnetic waves on the oppositeside of the portion 20. The emitted beam is correlated with a signal ofemitted intensity I₀ and the received beam generates a signal ofreceived intensity I_(R) The calculation unit 14 receives, in a timesequence with constant intervals, the values of the received intensityI_(R) for a constant emitted intensity I₀. In practice, the absorption Ais equal to the emitted intensity I₀ minus the received intensity I_(R).

[0030] The measurement of the hemoglobin concentration HGB is based onstudies carried out by the applicant, who, by means of experimentaltests, has correlated the hemoglobin concentration HGB with theabsorption A, in other words with the received intensity signal I_(R)for a constant emitted intensity signal I₀, as shown in the graph ofFIG. 1.

[0031] The applicant has determined the error of measurement of thehemoglobin concentration HGB as a function of the blood pressure P asshown in FIG. 3, as a function of the blood flow Q_(b) as shown in FIG.4, and as a function of temperature T as shown in FIG. 2.

[0032] The applicant's studies have demonstrated that the blood flowQ_(b), the pressure P, and the temperature T modify the blood's capacityfor absorption (A) of electromagnetic radiation, in other words theabsorption A, and cause a deviation between the values of hemoglobinconcentration HGB found in the machine and those found in laboratorytests.,, In other words, the physical quantities acting on the bloodduring the operation of the machine 1 cause structural modifications ofthe red corpuscles, which, although small, are sufficient to alter themeasurement of the hemoglobin concentration HGB. In particular, when thepressure P increases the red corpuscles are flattened, while the flowQ_(b) causes an orientation of the red corpuscles and the temperature Tcauses a change in the dimensions of the corpuscles.

[0033] Measurements were made on the basis of the studies carried out bythe applicant, and by means of the measuring device 9, and theiraccuracy was found to increase with an increase in the allowance madefor the physical quantities which modify the structure of the redcorpuscles.

[0034] The value of the internal diameter Di is set in the calculationunit 14, which receives the value of the flow Q_(b) and calculates thehemoglobin concentration HGB as a function of the values of absorption Aof electromagnetic waves, of the pressure values P measured by thesensor 12, of the flow Q_(b) Of the pump 8, and of the values T measuredby the sensor 13.

[0035] In practice, the following function relating the hemoglobinconcentration to the aforesaid quantities was calculated on the basis ofthe studies which were carried out:${HGB} = {\left( {\ln \frac{I_{R}}{I_{0}}} \right) \cdot {f\left( {Q_{i},\quad P{{\left. {,{{Di}{\quad,}\quad T}} \right) = {\left\lbrack {\ln \left( {1 - \frac{A}{I_{0}}} \right)} \right\rbrack \cdot {f\left( {Q_{B}{,\quad}\quad P,\quad {Di},\quad T} \right)}}}\quad}}\quad \right.}}$

[0036] This function can also be simplified, since eliminating thedependence on one or two of the measured physical quantities, consistingof the pressure P, the flow Q_(b) and the temperature T, will provide ameasurement of the hemoglobin concentration HGB which is less accuratethan the measurement in which the function takes into account all threeof the measured physical quantities, but is still more accurate than ameasurement based solely on the absorption A, and is closer to thelaboratory measurements.

[0037] The structure and functional working of the connection 10 isimportant in order to properly compensate the measurement of HGB as afunction of the pressure. Indeed the amplitude, period and variablecomponents of pressure in the tube 15 (the pressure is constantlymodulated by the blood pump 8) influence the HGB measurement. Since thetube 15 and the chamber 16 are directly engaged one another and bothmade of rigid material the pressure detection in the chamber 16 is veryprecise and strictly related to the pressure and to the pressurevariations in tube 15. Moreover, given the close proximity between tube15 and chamber 16 and the rigidity of connection 10, it is practicallyimpossible to deform the blood conduit between the section where theoptical detection is carried out and the section where the pressuredetection is obtained. The axial distance between the cross section ofthe portion 20 of tube 15 where the optical detection is carried out andthe cross section of chamber 16 where the pressure detection is obtainedshall be less than 50 mm; in the embodiment shown in the FIGS. 6 and 7such a distance is equal to 25 mm. The portion 20 of tube 15 shallpresent an internal diameter Di less than 10 mm.

[0038] With reference to FIGS. 8 and 9, the graphs show a curve of theintensity I_(R) received by the detector 27 as a function of time t anda curve of the values of the variance VAR of the curve of receivedintensity I_(R) as a function of time t.

[0039] With reference to FIG. 8, the curve of the values of I_(R)comprises a first section 28, which is characterized by a cyclicalvariation of the values of I_(R) caused by the flow Q_(b) provided bythe peristaltic pump 8 and corresponds to a normal stage of operation ofthe dialysis machine 1, and a section 29 which corresponds to a stage inwhich a blockage of the circuit has occurred up-line from the sensor 11.Although the divergence between the values of I_(R) of the section 28and those of the section 29 is significant in graphic terms, it isdifficult, in terms of the signal, to establish a threshold whichclearly distinguishes the section 28 from the section 29. Conversely,the variance VAR shows a peak tending towards infinity at the point ofthe change from the section 28 to the section 29, in other words at theinstant when the blockage of the circuit 2 occurs.

[0040] With reference to FIG. 9, the curve of the received intensityI_(R) comprises a first section 30 which corresponds to a stage ofnormal operation of the machine 1, and a section 31 which corresponds toa stage in which a blockage of the circuit has occurred down-line fromthe sensor 11, which does not cause a significant variation of thereceived intensity I_(R). Conversely, the down-line blockage causes asignificant variation of the variance VAR as a function of time t.

[0041] The calculation unit 14 constantly compares each value of thevariance VAR with a range of acceptability in the region of a mean valueof the values of variance VAR corresponding to the normal operation ofthe machine 1, in other words without blockages of the circuit 2. If thevalue of the variance VAR diverges significantly from the range ofacceptability, the calculation unit 14 emits an error signal E.

[0042] Consequently, the measurement of the absorption A is used notonly to measure the hemoglobin concentration HGB, but also to discoverwhether a blockage has occurred up-line or down-line from the sensor 11in the arterial branch 5.

1) Method of measuring the hemoglobin concentration (HGB) in the bloodin a circuit (2) of a dialysis machine (1), the method comprising themeasurement of the values of absorption (A) of electromagnetic waves bythe blood along one section (5 a) of the said circuit (2), the values ofthe said absorption (A) being correlated with the values of the saidhemoglobin concentration (HGB); the method being characterized in thatthe values of at least one physical quantity of the blood, from thegroup comprising blood pressure (P), blood temperature (T) and the rateof flow (Q_(b)) of blood along the said section (5 a), are measured, andthe values of hemoglobin concentration (HGB) in the blood are calculatedas a function of the values of absorption (A) and of the said physicalquantity. 2) Method according to claim 1, characterized in that thevalues of the hemoglobin concentration (HGB) are calculated as afunction of the values of absorption (A) and the values of pressure (P)measured along the said section (5 a). 3) Method according to claim 1,characterized in that the values of the hemoglobin concentration (HGB)are calculated as a function of the values of absorption (A) and thevalues of flow rate (Q_(b)) along the said section (5 a). 4) Methodaccording to claim 1, characterized in that the values of the hemoglobinconcentration (HGB) are calculated as a function of the values ofabsorption (A) arid the values of temperature (T) measured along thesaid section (5 a). 5) Method according to claim 1, characterized inthat the said section (5 a) is located down-line from a peristaltic pump(8) providing a specified rate of flow (Q_(b)) of blood, the values ofhemoglobin concentration (HGB) being calculated as a function of thevalues of absorption (A), the values of pressure (P) and the values offlow rate (Q_(b)). 6) Method according to claim 1, characterized in thatthe said section (5 a) is located down-line from a peristaltic pump (8)providing a specified rate of flow (Q_(b)) of blood, the values ofhemoglobin concentration (HGB) being calculated as a function of thevalues of absorption (A), the values of pressure (P) and the values offlow rate (Q_(b)) and the values of temperature (T). 7) Method accordingto one of the preceding claims, characterized in that the said section(5 a) comprises a portion (20) of a tube (15), said electromagneticwaves passing through the said portion (20) along a specified path. 8)Method according to claim 7, characterized in that the said path iscorrelated with the internal diameter (Di) of the said portion (20). 9)Method according to claim 8, characterized in that the saidcharacteristic (HGB) of the blood is calculated as a function of theinternal diameter (Di) of the said portion (20). 10) Method according toone of claims 1 to 9, characterized in that the absorption (A) ismeasured by means of a sensor (11) located in the said section (5 a),comprising an emitter (26) for emitting a beam of electromagnetic waveswith a specified emission intensity (I₀) and a detector (27) which candetect a received intensity (I_(R)), the said absorption (A) being equalto the difference between the emission intensity (10) and the receivedintensity (I_(R)). 11) Method according to claim 10, characterized inthat the variance (VAR) of the received intensity (I_(R)) is calculated,and the variance (VAR) is compared with a range of acceptability todetect an interruption up-line and/or down-line from the said section (5a). 12) Method according to claim 1, characterized in that an errorsignal (E) is emitted if the value of the variance (VAR) is outside thesaid range of acceptability. 13) Blood circulation circuit for adialysis machine, preferably for the application of the method accordingto one of claims 1 to 12, characterized in that it comprises aconnection (10) forming the said section (5 a) of the circuit (2), thesaid connection comprising a tube . (15) for subjecting the blood to themeasurement of the absorption (A) of electromagnetic waves and a chamber(16) for subjecting the blood to the measurement of pressure (P). 14)Circuit according to claim 13, characterized in that the said chamber(16) is covered by a deformable membrane (24). 15) Circuit according toclaim 13 or 14, characterized in that it comprises an arterial branch(5) and a venous branch (6), the said connection (10) being locatedalong the arterial branch (5). 16) Circuit according to claim 13,characterized in that the tube (15) and the chamber (16) are directlyengaged one another. 17) Circuit according to claim 13, characterized inthat the tube (15) and the chamber (16) are both made of rigid material.18) Circuit according to claim 13, characterized in that the tube (15)presents a portion (20) defining a first measurement cross section wherethe absorption measurement is carried out, and the chamber (16) presentsa second measurement cross section where pressure detection is obtained,the distance between said measurement cross sections being less then 50mm. 19) Circuit according to claim 13, characterized in that the portion(20) presents an internal diameter Di less than 10 mm 20) Device formeasuring the hemoglobin concentration in a circuit (2) of a dialysismachine (1) comprising a connection (10) forming a section (5 a) of thesaid circuit (2), the said connection (10) comprising a tube (15) alongwhich a measurement is made by means of beams of electromagnetic wavesto determine the absorption (A) of the blood, the hemoglobinconcentration (HGB) being correlated with the said absorption (A), thedevice being characterized in that it comprises at least one furthersensor (12, 13) for measuring one of two quantities, namely the bloodpressure (P) and the blood temperature (T); the hemoglobin concentration(HGB) being a function of the absorption (A) and of the said quantity.21) Device according to claim 20, characterized in that the pressuresensor (12) comprises a chamber (16) fitted with a deformable membrane(24) to measure the variations of pressure (P) of the blood by means ofan electrical device (25) in the said section (5 a), the hemoglobinconcentration (HGB) of the blood being a function of the absorption (A)of the blood and of the pressure (P). 22) Device according to claims 20and 21, characterized in that it comprises a temperature sensor (13)located in the said connection (10). 23) Device according to one ofclaims 20 to 22, characterized in that the said connection (10) islocated down-line from a peristaltic pump (8) providing a specified rateof flow (Q_(b)) of blood, the hemoglobin concentration (HGB) beingcalculated as a function of the rate of flow (Q_(b)) of the blood. 24)Device according to claim 21, characterized in that the said tube (15)and the said chamber (16) are made from transparent rigid material. 25)Device according to claim 21, characterized in that it comprises asensor (11) located on the said tube (15), the sensor (11) comprising anemitter (26) for emitting a beam of electromagnetic waves with aspecified emission intensity (10) and a detector (27) which can detectthe received intensity (I_(R)), the said absorption (A) being equal tothe difference between the emission intensity (10) and the receivedintensity (I_(R)). 26) Device according to claim 25, characterized inthat it comprises a calculation unit (14) connected to the said sensors(11, 12, 13) and to the said peristaltic pump (8).